Visual PROTACPROTAC Design Principles
PROteolysis-Targeting Chimeras (PROTACs) are heterobifunctional molecules that recruit an E3 ubiquitin ligase to a target protein, leading to its ubiquitination and degradation. Visual PROTAC supports calculation and visualization for PROTAC design.
Ternary complex
A PROTAC forms a ternary complex: target protein · PROTAC · E3 ligase. Effective degradation depends on the stability and geometry of this complex. Design aims to optimize binding to both the target and the E3, and linker length/flexibility to allow productive orientation.
Warhead and E3 ligand
The target-binding warhead and the E3-binding ligand are connected by a linker. Warheads are often small-molecule inhibitors of the target; E3 ligands recruit specific E3 ligases (e.g. VHL, CRBN). Molecular weight and physicochemical properties of each moiety affect cell permeability and selectivity.
Linker
Linker length and flexibility influence ternary complex formation and degradation efficiency. Too short or too rigid linkers may prevent productive binding; too long or too flexible may reduce effective concentration. Use the Linker Library to explore common linkers (PEG, cleavable, etc.) and the PROTAC Molecular Weight tool to compute combined MW and properties. Use the 3D Viewer to inspect conformations (Ternary Complex Assembly, Linker Conformation).
Using Visual PROTAC
Calculate PROTAC molecular weight and properties, visualize ternary complex assembly, and export structures for further analysis. Data sources include PROTAC-DB, PDB, ChEMBL, and PubChem.